Substance P-mediated expression of the pro-angiogenic factor CCN1 modulates the course of colitis
| Autor: | Alan C. Moss, Collin Bowe, Charalabos Pothoulakis, Dezheng Zhao, Hua Xu, Hon Wai Koon, Mary Pat Moyer |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Angiogenesis Colon Inflammation Biology Substance P Inflammatory bowel disease Immediate early protein Pathology and Forensic Medicine Immediate-Early Proteins Mice Crohn Disease Cell Movement medicine Animals Humans Colitis Integrin alphaVbeta3 Neovascularization Pathologic Microcirculation Dextran Sulfate Endothelial Cells Receptors Neurokinin-1 medicine.disease Bridged Bicyclo Compounds Heterocyclic Ulcerative colitis Endothelial stem cell Mice Inbred C57BL Immunology Cancer research Intercellular Signaling Peptides and Proteins Colitis Ulcerative Endothelium Vascular medicine.symptom Cysteine-Rich Protein 61 Regular Articles |
| Zdroj: | The American journal of pathology. 173(2) |
| ISSN: | 1525-2191 |
| Popis: | Substance P (SP) regulates important intestinal functions, such as mucosal permeability, motility, chloride secretion, and inflammation via the neurokinin-1 receptor (NK-1R). Previous reports showed that vascularization and expression of angiogenic factors are evident in the colonic mucosa of rats with colitis and patients with inflammatory bowel disease. Here we determined whether SP is associated with angiogenesis. Human NCM460 colonocytes stably transfected with the human NK-1R (NCM460-NK-1R cells) and mice with dextran sodium sulfate-induced colitis were used. We found that expression of the angiogenic factor CCN1 was increased in the colons of patients with Crohn's disease and ulcerative colitis. Mucosal extracts from inflammatory bowel disease patients induced human intestinal microvascular endothelial cell migration that was inhibited by blockade of CCN1 and its receptor integrin alphavbeta3. Both the degree of angiogenesis and CCN1 expression were elevated in the colons of mice with dextran sodium sulfate-induced colitis, which was reduced by treatment with the NK-1R antagonist CJ-12255. SP also increased CCN1 expression in NCM460-NK-1R colonocytes. SP exposure to human intestinal microvascular endothelial cells co-cultured with NCM460-NK-1R cells induced angiogenic activity that was inhibited by CCN1 silencing. In addition, intracolonic overexpression of CCN1 induced angiogenesis in mouse colon. Thus, SP mediates angiogenesis via CCN1 during colitis. |
| Databáze: | OpenAIRE |
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